@article {Ametamey698, author = {Simon M. Ametamey and Lea J. Kessler and Michael Honer and Matthias T. Wyss and Alfred Buck and Samuel Hintermann and Yves P. Auberson and Fabrizio Gasparini and Pius A. Schubiger}, title = {Radiosynthesis and Preclinical Evaluation of 11C-ABP688 as a Probe for Imaging the Metabotropic Glutamate Receptor Subtype 5}, volume = {47}, number = {4}, pages = {698--705}, year = {2006}, publisher = {Society of Nuclear Medicine}, abstract = {11C-ABP688 (3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent. Methods: ABP688 was radiolabeled with 11C by reacting 11C-methyl iodide with the sodium salt of desmethyl-ABP688 (3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone oxime). The affinity of 11C-ABP688 for mGluR5 was determined by Scatchard analysis using rat whole-brain membranes (without cerebellum). Ex vivo autoradiography, biodistribution, and PET studies with 11C-ABP688 were performed on rats, wild-type mice, and mGluR5-knock-out mice. Results: The overall synthesis time was 45-50 min from the end of radionuclide production. 11C-ABP688 was obtained in good radiochemical yield (35\% {\textpm} 8\%, n = 17, decay corrected), and the specific radioactivity was 150 {\textpm} 50 GBq/μmol (n = 17) at the end of the synthesis. Scatchard analysis revealed a single high-affinity binding site with a dissociation constant of 1.7 {\textpm} 0.2 nmol/L and a maximum number of binding sites of 231 {\textpm} 18 fmol/mg of protein. Ex vivo autoradiography in wild-type mice and rats showed a heterogeneous distribution pattern consistent with the known distribution of mGluR5 in the brain, with the highest uptake in hippocampus, striatum, and cortex. Blocking studies by coinjection of 11C-ABP688 and unlabeled 2-methyl-6-(3-methoxyphenyl)ethynyl-pyridine (1 mg/kg), an antagonist for mGluR5, revealed up to 80\% specific binding in rat brain. In mGluR5-knock-out mouse brain, a homogeneous and markedly reduced accumulation of 11C-ABP688 was observed. PET studies on rats and mice using a small-animal PET scanner also demonstrated radioactivity uptake in the brain regions known to be rich in mGluR5. In contrast, radioactivity uptake in mGluR5-knock-out mice was fairly uniform, substantiating the specificity of 11C-ABP688 binding to mGluR5. Conclusion: 11C-ABP688 is a selective tracer for imaging mGluR5 in vivo in rodents and may offer a future tool for imaging mGluR5 in humans using PET.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/47/4/698}, eprint = {https://jnm.snmjournals.org/content/47/4/698.full.pdf}, journal = {Journal of Nuclear Medicine} }